Nanoparticles exhibit size-dependent physical and chemical properties, such as reduced melting point and increased reactivity and solubility. These special properties of nanoparticles are often due to their large surface area. The increase in solubility of nanosized material is a thermodynamic effect that results from the increased chemical potential at a curved surface.
In a typical RESS (rapid expansion of supercritical solutions) process, supercritical fluid is used to dissolve solid material under high pressure and temperature, thus forming a homogeneous supercritical phase. Thereafter, the solution is expanded through a nozzle, and small particles are formed. At the rapid expansion point right at the opening of the nozzle, there is a sudden pressure drop that forces the dissolved material to precipitate out of the solution. The crystals that are instantly formed enclose a small amount of the solvent that, due to the expansion, changes from supercritical fluid to its normal state, thus breaking the crystal from inside-out. The particles that are formed this way may have a diameter of a few hundreds of nanometers.
Supercritical fluid processing techniques have shown promise in production of small particles of water-insoluble materials. For example WO 97/14407 and WO 99/65469 describe processes that generate submicron-size particles of biologically useful materials through the use of supercritical or compressed fluid processing techniques. However, these processes produce particle suspensions containing a substantial fraction of drug particles larger than 100 nm. Substantially smaller particles would be advantageous for medical applications. The process was further developed in WO 2006/015358 that discloses a method to prepare homogenous aqueous suspensions of nanoscale drug particles with the aid of stabilizing agents. According to the process disclosed in WO 2006/015358, all the formed particles are smaller than 100 nm, and standard deviation of particle size was less than 15 nm.
WO 97/31691 discloses a method and apparatus for particle precipitation and coating, wherein the precipitable substance is in contact with a supercritical antisolvent together with an energizing gas stream to generate focused high frequency sonic waves in the antisolvent to break the particles into smaller ones. The size or the particles obtained using the technology was 0.1-10 μm.
U.S. Pat. No. 7,815,426 discloses an apparatus and method for preparing nanoparticles wherein a suspension of an organic substance is passed through a micro flow channel, and the organic substance is irradiated with a laser beam.
US 2006/0153921 disclosed a method of producing particles from solution-in-supercritical fluid or compressed gas emulsions. According to this disclosure, a solution including a solute dissolved in a solvent is contacted with supercritical fluid or compressed gas to for a solution-in supercritical fluid or compressed gas emulsion. The emulsion is sprayed through an orifice to create spray droplets from which the supercritical fluid or compressed gas is removed resulting in the formation of particles that include the solute. Finally, the solvent is removed e.g. by evaporation.
A typical RESS is a two-step process. The first step is an extraction or solvation in which a supercritical fluid is saturated with the substrates of interest. This extraction is followed by a sudden depressurization through [PJJ1] a nozzle which produces a large decrease in the solvent power and the temperature of the fluid, therefore causing the precipitation of the solute. Key parameters of RESS process are the pre-expansion pressure and temperature, the expansion pressure, and the nozzle design. An approximate pressure profile in a RESS process is shown in FIG. 1. As the ratio between the pre-expansion pressure (A) and the expansion pressure (C) are typically very high, sonic velocities are achieved at the outlet of the nozzle, and a supersonic jet that ends at the Mach disc is formed. Most of the pressure drop is produced at a supersonic free jet (C). The pressure in this region can be below the bulk pressure of the expansion vessel (D). This depressurization also causes drastic decrease in temperature, which can lead to CO2 condensation or freezing. At the end of supersonic region a Mach shock is formed and the pressure is increases up to the ambient pressure, accompanied by an increase in temperature.
Since in a RESS process scCO2 is expanded through the capillary nozzle, first possible pressure reduction (B) takes place in the capillaries of the nozzle. Nucleation may start in the nozzle capillaries, due to small pressure reduction. The greater pressure reduction takes place as the fluid such as CO2 enters the collection chamber and thus most of the nucleation takes place there.
Accordingly, in a RESS process nucleation takes mainly place after the exit nozzle. Due to the sudden pressure drop from the pre-expansion pressure to the post-expansion pressure, the supersaturation level is high and number of nuclei formed is large and the size of these nuclei small. The nuclei are grown mainly by coagulation in the collection chamber. Coagulation is caused by the high flow velocities and the density differences, caused by Mach disk formation, in the collection chamber.
Since nanoparticles find many potential applications and, since there is a limited number of processes to produce them, there is a need to develop new methods to prepare such particles.